Reply to Letter to the Editor "Free Drug Fraction Versus Free Drug Concentration"

Letter to the Editor

Sir: We thank Dr. Pies for his thoughtful comments andagree that the free, non-protein-bound concentration of drugs inplasma is more closely correlated with drug effect than totalconcentration. In addition, for many drugs and situations, includingdrug-drug interactions that result in displacement ofdrugs from plasma protein binding sites, the increase in freedrug concentration is transient. An exception to this generalizationwould be a drug with a high hepatic intrinsic clearancewhose plasma protein binding is nonrestrictive for eliminationand that is administered intravenously.